Priming the Surface of Orthopedic Implants for Osteoblast Attachment in Bone Tissue Engineering

The development of better orthopedic implants is incessant. While current implants can function reliably in the human body for a long period of time, there are still a significant number of cases for which the implants can fail prematurely due to poor osseointegration of the implant with native bone. Increasingly, it is recognized that it is extremely important to facilitate the attachment of osteoblasts on the implant so that a proper foundation of extracellular matrix (ECM) can be laid down for the growth of new bone tissue. In order to facilitate the osseointegration of the implant, both the physical nanotopography and chemical functionalization of the implant surface have to be optimized. In this short review, however, we explore how simple chemistry procedures can be used to functionalize the surfaces of three major classes of orthopedic implants, i.e. ceramics, metals, and polymers, so that the attachment of osteoblasts on implants can be facilitated in order to promote implant osseointegration.     

The effect of collagen I mimetic peptides on mesenchymal stem cell adhesion and differentiation,and on bone formation at hydroxyapatite surfaces

Integrin-binding peptides increase cell adhesion to naive hydroxyapatite (HA), however, in the body, HA becomes rapidly modified by protein adsorption. Previously we reported that, when combined with an adsorbed protein layer, RGD peptides interfered with cell adhesion to HA. In the current study we evaluated mesenchymal stem cell (MSC) interactions with HA disks coated with the collagen-mimetic peptides, DGEA, P15 and GFOGER. MSCs adhered equally well to disks coated with DGEA, P15, or collagen I, and all three substrates, but not GFOGER, supported greater cell adhesion than uncoated HA. When peptide-coated disks were overcoated with proteins from serum or the tibial microenvironment, collagen mimetics did not inhibit MSC adhesion, as was observed with RGD, however neither did they enhance adhesion. Given that activation of collagen-selective integrins stimulates osteoblastic differentiation, we monitored osteocalcin secretion and alkaline phosphatase activity from MSCs adherent to DGEA or P15-coated disks. Both of these osteoblastic markers were upregulated by DGEA and P15, in the presence and absence of differentiation-inducing media. Finally, bone formation on HA tibial implants was increased by the collagen mimetics. Collectively these results suggest that collagen-mimetic peptides improve osseointegration of HA, most probably by stimulating osteoblastic differentiation, rather than adhesion, of MSCs.     

The effect of plasma chemical oxidation of titanium alloy on bone-implant contact in rats

Many different technologies have been used to enhance osseointegration in orthopaedic and dental implant surgery. Hydroxyapatite coatings, pure or in combination with growth factors or bisphosphonates, showed improved osseointegration of titanium alloy implants. We choose a different approach to enhance osseointegration: plasma chemical oxidation was used to modify the surface of titanium alloy implants. This technique converts the nm-thin natural occurring titanium oxide layer on an implant to a 4?μm thick ceramic coating (TiOB surface). Bioactive TiOB surfaces have a macroporous structure and were loaded with calcium and phosphorus, while bioinert TiOB surfaces are smooth. A rat tibial model with bilateral placement of titanium alloy implants was employed to analyze the bone response to TiOB surfaces in?vivo. 64 rats were randomly assigned to four groups of implants: (1) titanium alloy (control), (2) titanium alloy, type III anodization, (3) bioinert TiOB surface and (4) bioactive TiOB surface. Mechanical fixation, peri-implant-bone area and bone contact were evaluated by pull-out tests and histology at three and eight weeks. Shear strength and bone contact at eight weeks were significantly increased in the bioactive TiOB group compared to all other groups. The results of plasma chemical oxidation in a rat model showed that the bioactive TiOB surface has a positive effect on implant anchorage by enhancing the bone-implant contact in normal bone.     

Primary human marrow stromal cells and Saos-2 osteosarcoma cells use different mechanisms to adhere to hydroxylapatite

One important step in bone formation on hard tissue implants is adhesion of osteoblast precursors to the implant surface. In this study, we used function-blocking antibodies against integrin subunits to characterize the mechanisms used by human marrow stromal cells and Saos-2 osteosarcoma cells to adhere to protein-coated hydroxylapatite (HA). We found that Saos-2 use both alpha5- and alphav-containing integrins, whereas stromal cells use alphav-containing integrins but not alpha5-containing integrins, despite the presence of alpha5-containing integrins on cell surfaces. On the basis of this difference, we examined binding of these cell types to HA coated with fibronectin (FN) or vitronectin (VN), to determine whether these ligands for alpha5 and alphav integrins could enhance the numbers or morphology of cells adhered to them. We also examined the adhesion of cells to HA coated with RGD peptides designed to bind to FN or VN receptors. Morphology and number of adherent stromal cells were markedly enhanced on serum-coated surfaces compared with FN or VN alone, whereas, surprisingly, Saos-2 cells failed to spread on serum-coated HA and displayed superior spreading and stress fiber formation on FN-coated [corrected] HA. Collectively, these results have important implications for the design of protein coatings to enhance the performance of HA implants.     

Histological analysis of bone/heteroplastic implant interfaces in dog tibia.

This work presents histological analysis of interfaces between bone and heteroplastic implants in dog tibias. The study was performed in four tibias (of four mongrel dogs) into which cylindrical implants were inserted. One ceramic (titania) implant and three grit-blasted titanium implants (with sandblasted and acid-corroded surfaces) were chosen for histological analysis of the implant surface/bone tissue interface. The implants remained in the tibias for eight months and none were loaded during this period. The animals were subsequently sacrificed and the samples were processed for analysis. Light microscope analysis revealed a large amount of osteoid tissue and proximity of osteoblasts and osteocytes to the implant surfaces. In addition, little or no fibrous tissue was observed between the bone and implant surfaces. The titanium implants presented better osseointegration than did the ceramic implant.     

The effect of the surface modification of titanium using a recombinant fragment of fibronectin and vitronectin on cell behavior

The surface of titanium implants is in direct contact with host tissue and plays a critical role in determining biocompatibility. Fibronectin (FN) and vitronectin (VN) are major cell adhesive proteins found in the extracellular matrix (ECM) of various tissues, and in circulating blood. The aim of this study was to evaluate the engineered biomimetic surface of titanium by using recombinant fragment of FN(8-10) and VN(NTD) that contains the binding site for integrins. MC3T3-E1 cells seeded upon the FN(8-10)-coated titanium showed a marked increase in cell adhesion, proliferation, and differentiation over VN(NTD)-coated titanium. In addition, we confirmed that the surface properties of titanium prefer for FN(8-10) over VN(NTD) (p<0.05) in protein adhesion. These results suggest that the FN(8-10)-modified titanium surface can be used to improve the osseointegration of titanium implants by enhancing bone formation.     

Tailored integrin-extracellular matrix interactions to direct human mesenchymal stem cell differentiation

Integrins provide the primary link between mesenchymal stem cells (MSCs) and their surrounding extracellular matrix (ECM), with different integrin pairs having specificity for different ECM molecules or peptide sequences contained within them. It is widely acknowledged that the type of ECM present can influence MSC differentiation; however, it is yet to be determined how specific integrin-ECM interactions may alter this or how they change during differentiation. We determined that human bone marrow-derived mesenchymal stem cells (hMSCs) express a broad range of integrins in their undifferentiated state and show a dramatic, but transient, increase in the level of α5 integrin on day 7 of osteogenesis and an increase in α6 integrin expression throughout adipogenesis. We used a nonfouling polystyrene-block-poly(ethylene oxide)-copolymer (PS-PEO) surface to present short peptides with defined integrin-binding capabilities (RGD, IKVAV, YIGSR, and RETTAWA) to hMSCs and investigate the effects of such specific integrin-ECM contacts on differentiation. hMSCs cultured on these peptides displayed different morphologies and had varying abilities to differentiate along the osteogenic and adipogenic lineages. The peptide sequences most conducive to differentiation (IKVAV for osteogenesis and RETTAWA and IKVAV for adipogenesis) were not necessarily those that were bound by those integrin subunits seen to increase during differentiation. Additionally, we also determined that presentation of RGD, which is bound by multiple integrins, was required to support long-term viability of hMSCs. Overall we confirm that integrin-ECM contacts change throughout hMSC differentiation and show that surfaces presenting defined peptide sequences can be used to target specific integrins and ultimately influence hMSC differentiation. This platform also provides information for the development of biomaterials capable of directing hMSC differentiation for use in tissue engineering therapies.     

The interface zone of inorganic implantsIn vivo: Titanium implants in bone

The interface zone between titanium implants and bone is considered at the macroscopic, microscopic, and molecular levels. A high rate of successful dental implants of pure titanium is associated with a very close apposition of the bone to the titanium surface, called osseointegration. At the macroscopic level, osseointegration allows efficient stress transfer from the implant to the bone without abrasion or progressive movement that can take place if a fibrous layer intervenes. At the microscopic level, surface roughness and porosity provide interlocking of the implant and bone tissue which grows into direct contact with titanium. Sections studied in the electron microscope show that calcified tissue can be identified within 50 Å of the implant surface. The interface zone includes a tightly adherent titanium oxide layer on the surface of the implant which may be similar to a ceramic material in relation to tissue response. The five year success rate of 90% in 2895 implants in clinical trials since 1965 is associated with the favorable behavior of bone tissue at the interface zone with pure titanium.     

Osseointegration of hydroxyapatite-coated and noncoated Ti6Al4V implants in the presence of local infection: a comparative histomorphometrical study in rabbits

A study was designed to investigate the osseointegration of titanium implants, either noncoated or coated with hydroxyapatite (HA), into rabbit tibiae in the presence of local infection compared with osseointegration in the absence of local infection. HA-coated or noncoated Ti cylinders were implanted into both tibiae of 32 rabbits (New Zealand Whites). Before implantation the left tibia was contaminated with different quantities of Staphylococcus aureus (10(2)-10(5) CFU). Four weeks after surgery the tibiae were explanted and prepared for microbiological and histomorphometrical examination. Histomorphometrical data, as a representation of implant fixation, were obtained by measuring the percentage of bone around the implants (within a radius of 1 mm from the outer diameter of the implants) and the percentage of the circumference of the implant that was in direct contact with bone. Histomorphometry revealed, in particular for the HA implants, a relationship between the inoculum concentration and/or the presence or absence of infection with the bone contact at the distal implant side. This confirms a relationship between peri-implant infection and bone contact or remodeling. HA-coated implants developed, in the presence of bacteria, more easily a more severe infection than noncoated Ti implants, and we show in the present study that local infection will influence histomorphometrical parameters (bone-implant contact) that determine implant fixation. Precautions to prevent contamination (asepsis) and/or infection (perioperative antibiotics) are even more important for the highly biocompatible HA-coated implant.     

Biomolecular surface coating to enhance orthopaedic tissue healing and integration

Implant osseointegration is a prerequisite for clinical success in orthopaedic and dental applications, many of which are restricted by loosening. Biomaterial surface modification approaches, including calcium-phosphate ceramic coatings and macro/microporosity, have had limited success in promoting integration. To improve osseointegration, titanium surfaces were coated with the glycine-phenylalanine-hydroxyproline-glycine-glutamate-arginine (GFOGER) collagen-mimetic peptide, selectively promoting alpha2beta1 integrin binding, a crucial event for osteoblastic differentiation. Titanium surfaces presenting GFOGER triggered osteoblastic differentiation and mineral deposition in bone marrow stromal cells, leading to enhanced osteoblastic function compared to unmodified titanium. Furthermore, this integrin-targeted coating significantly improved in vivo peri-implant bone regeneration and osseointegration, as characterized by bone-implant contact and mechanical fixation, compared to untreated titanium in a rat cortical bone-implant model. GFOGER-modified implants also significantly enhanced osseointegration compared to surfaces modified with full-length type I collagen, highlighting the importance of presenting specific biofunctional domains within the native ligand. In addition, this biomimetic implant coating is generated using a simple, single-step procedure that readily translates to a clinical environment with minimal processing and cytotoxicity concerns. Therefore, this study establishes a biologically active and clinically relevant implant-coating strategy that enhances bone repair and orthopaedic implant integration.     

Transforming growth factor-beta1 incorporated during setting in calcium phosphate cement stimulates bone cell differentiation in vitro

Growth stimulation of periimplant tissues by growth factors like transforming growth factor-beta1 (TGF-beta1) may increase the indication for and success of implant use. Calcium phosphate as a material for implants or for coating of implants is known for its good biologic interaction with bone. Therefore, calcium phosphate implants combined with TGF-beta1 might improve osseointegration. In this study we hypothesise that the addition of recombinant human TGF-beta1 (rhTGF-beta1) to calcium phosphate cement (CPC) affects the differentiation of bone cells growing on the cement layer. rhTGF-beta1 incorporated during setting in a CPC layer at 20 ng rhTGF-beta1/60 mg cement was found to be gradually released into tissue culturing medium leading to a 20% release after 24 h. Two cell populations were obtained from collagenase-treated fragments of adult rat long bones: preosteoblastic cells, which were released by the collagenase treatment, and osteoblastic cells, which grew from the collagenase-stripped bone fragments. Both cell populations were tested for their osteoblastic characteristic phenotype by measuring their alkaline phosphatase (ALP) activity after vitamin D treatment and cyclic AMP after parathyroid hormone stimulation. After preculture the cells were plated on a layer of CPC containing 0 (control), 10, or 20 ng rhTGF-beta1/60 mg CPC. Bone cell differentiation was analyzed after 10 days by measuring the ALP activity, as well as the protein content of the cell layer. Incorporation of rhTGF-beta1 in the CPC did not change the ALP activity in osteoblastic cells, but a significant (analyzed by multivariate analysis of variance) increase was observed in preosteoblastic cells. Incorporation of 10 ng of rhTGF-beta1 in 60 mg of CPC increased the ALP activity in preosteoblastic cells by threefold and 20 ng rhTGF-beta1/60 mg CPC increased it by fivefold. The total protein content was not affected by rhTGF-beta1 in either of the cell populations. We conclude that rhTGF-beta1 incorporated during setting in CPC stimulates the differentiation of preosteoblastic cells in vitro. These results provide a basis for further studies on the use of this combination as an implant material in vivo.     

The effect of integrin-specific bioactive coatings on tissue healing and implant osseointegration

Implant osseointegration, defined as bone apposition and functional fixation, is a requisite for clinical success in orthopaedic and dental applications, many of which are restricted by implant loosening. Modification of implants to present bioactive motifs such as the RGD cell-adhesive sequence from fibronectin (FN) represents a promising approach in regenerative medicine. However, these biomimetic strategies have yielded only marginal enhancements in tissue healing in vivo. In this study, clinical-grade titanium implants were grafted with a non-fouling oligo(ethylene glycol)-substituted polymer coating functionalized with controlled densities of ligands of varying specificity for target integrin receptors. Biomaterials presenting the alpha5beta1-integrin-specific FN fragment FNIII 7-10 enhanced osteoblastic differentiation in bone marrow stromal cells compared to unmodified titanium and RGD-presenting surfaces. Importantly, FNIII 7-10-functionalized titanium significantly improved functional implant osseointegration compared to RGD-functionalized and unmodified titanium in vivo. This study demonstrates that bioactive coatings that promote integrin binding specificity regulate marrow-derived progenitor osteoblastic differentiation and enhance healing responses and functional integration of biomedical implants. This work identifies an innovative strategy for the rational design of biomaterials for regenerative medicine.     

The effect of enzymatically degradable IPN coatings on peri-implant bone formation and implant fixation

Short-term osseointegration of orthopedic implants is critical for the long-term stability of the implant-bone interface. To improve initial implant stability, one strategy under consideration involves the presentation of adhesion ligands on the implant surface to stimulate bone regeneration in the peri-implant region. To assess the relative effects of implant surface chemistry and topography on osseointegration within the rat femoral ablation implant model, a nonfouling, enzymatically degradable interpenetrating polymer network (edIPN) of poly(AAm-co-EG/AAc) amenable to presenting the cell signaling domain Arg-Gly-Asp (RGD), was developed. Moderate enhancement of peri-implant bone formation was found after 28 days using the edIPN without peptide modification (p = 0.032). However, no data supported a benefit of peptide modification, as bone-implant contact, normalized bone volume and normalized fixation strength was equivalent or poorer than dual acid-etched (DAE) treated implants after 28 days. Surface topography was determined to be the dominant factor in modulating osseointegration, as DAE implants produced equivalent roughness-normalized fixation strength versus previously reported data on plasma-sprayed hydroxyapatite/tricalcium phosphate-coated implants (Barber et al., J Biomed Mater Res A, forthcoming). An ideal osseointegrated implant will require optimization of all three aforementioned parameters, and may take the form of biomolecule delivery from thin degradable polymer networks.     

RGD-coated titanium implants stimulate increased bone formation in vivo

Numerous studies have demonstrated that peptide modified surfaces influence short- and long-term cell responses such as attachment, shape and function in vitro. These responses are mediated via cell receptors known as integrins which bind specifically to short peptide sequences from larger proteins. Integrins transduce information to the nucleus through several cytoplasmic signalling pathways. Little is known, however, about the ability of peptide-coated surfaces to influence cell responses in vivo. The present study was designed to evaluate the quality and quantity of the new bone formed in response to titanium rods surface-coated with the peptide sequence Arg-Gly-Asp-Cys (RGDC) using gold-thiol chemistry and implanted in rat femurs. Histomorphometric analysis of cross-sections perpendicular to the implant long axis showed a significantly thicker shell of new bone formed around RGD-modified versus plain implants at 2 weeks (26.2 +/- 1.9 vs. 20.5 +/- 2.9 microm; P < 0.01). A significant increase in bone thickness for RGD implants was also observed at 4 weeks while bone surrounding controls did not change significantly in thickness (32.7 +/- 4.6 vs. 22.6 +/- 4.0 microm; P < 0.02). Mechanical pull-out testing conducted at 4 weeks revealed the average interfacial shear strength of peptide modified rods was 38% greater than control rods although this difference was not statistically significant. These pilot data suggest that an RGDC peptide coating may enhance titanium rod osseointegration in the rat femur. Long-term studies and evaluation of other peptides in larger animal models are warranted.     

The bone response of oxidized bioactive and non-bioactive titanium implants

A number of experimental and clinical data on so-called oxidized implants have reported promising outcomes. However, little is investigated on the role of the surface oxide properties and osseointegration mechanism of the oxidized implant. Sul [On the Bone Response to Oxidized Titanium Implants: The role of microporous structure and chemical composition of the surface oxide in enhanced osseointegration (thesis). G?teborg: Department of Biomaterials/Handicap Research, University of G?teborg, Sweden; 2002; Biomaterials 2003; 24: 3893-3907] recently proposed two action mechanisms of osseointegration of oxidized implants, i.e. mechanical interlocking through bone growth in pores/other surface irregularities (1) and biochemical bonding (2). The aim of the present study is two-fold: (i) investigating the role of the implant surface chemistry on bone responses; (ii) investigating the validity of the biochemical bonding theory of the oxidized, bioactive bone implants with specific implant surface chemistry. Two groups of oxidized implants were prepared using micro arc oxidation process and were then inserted in rabbit bone. One group consisted of magnesium ion incorporated implants (MgTiO implant), the other consisted of TiO2 stoichiometry implants (TiO implant). Surface oxide properties of the implants were characterized with various surface analytic techniques. After 6 weeks of follow up, the mean peak values of removal torque of Mg implants dominated significantly over TiO implants (p < or = 0.0001). Bonding failure generally occurred in the bone away from the bone to implant interface for the MgTiO implant and mainly occurred at the bone to implant interface for the TiO implant that consisted mainly of TiO2 chemistry and significantly rougher surface as compared to the MgTiO implant. Between bone and the Mg- incorporated implant surface, ionic movements and ion concentrations gradient were detected. The current in vivo experimental data may provide positive evidence for the surface chemistry-mediated biochemical bonding theory of oxidized bioactive implants. However, the present study does not rule out potential synergy effects of the oxide thickness, micro-porous structure, crystal structure and surface roughness on improvements of bone responses to oxidized bioactive implants.     

Histological and three-dimensional evaluation of osseointegration to nanostructured calcium phosphate-coated implants

Nanostructures on implant surfaces have been shown to enhance osseointegration; however, commonly used evaluation techniques are probably not sufficiently sensitive to fully determine the effects of this process. This study aimed to observe the osseointegration properties of nanostructured calcium phosphate (CaP)-coated implants, by using a combination of three-dimensional imaging and conventional histology. Titanium implants were coated with stable CaP nanoparticles using an immersion technique followed by heat treatment. Uncoated implants were used as the control. After topographical and chemical characterizations, implants were inserted into the rabbit femur. After 2 and 4weeks, the samples were retrieved for micro-computed tomography and histomorphometric evaluation. Scanning electron microscopy evaluation indicated that the implant surface was modified at the nanoscale by CaP to obtain surface textured with rod-shaped structures. Relative to the control, the bone-to-implant contact for the CaP-coated implant was significantly higher at 4weeks after the implant surgery. Further, corresponding 3-D images showed active bone formation surrounding the implant. 3-D quantification and 2-D histology demonstrated statistical correlation; moreover, 3-D quantification indicated a statistical decrease in bone density in the non-coated control implant group between 2 and 4weeks after the surgery. The application of 3-D evaluation further clarified the temporal characteristics and biological reaction of implants in bone.     

The effect of oxytocin on osseointegration of titanium implant in ovariectomized rats

Introduction: Oxytocin (OT) was reported to control differentiation of human mesenchymal stem cells and reverse osteoporosis (OP). This study investigated the effect of systematical treatment of OT on implant osseointegration in ovariectomized (OVX) rats. Material and methods: Twenty female rats received bilateral ovariectomy. Twelve weeks later, all animals were randomly assigned to control or experimental group. Each rat received two implants at the distal femoral metaphysis. From the first postoperative day, rats in experiment group received subcutaneous injection of OT (1 mg/kg · d), while animals in control group received vehicle. Twelve weeks after implantation, specimens containing implants were harvested and evaluated by histology, micro-CT, and push-out test. Tibiae were also harvested to evaluate the effect of OT on intact bone tissue of OVX rats. Results: Compared with control, OT treatment increased the relative bone volume surrounding the implant by 2.2 times, the percent implant osseointegration by 0.62 times, and the maximum push-out force by 2.25 times. Increased bone mass was also observed in histological sections of distal femur with implant and intact bone tissue of the proximal tibiae. Conclusion: Systemic administration of OT promoted peri-implant bone healing and osseointegration of titanium implant and recovered the negative effects of OP in undisturbed bone tissue partially.     

Effects of bone morphogenetic protein-2 and hyaluronic acid on the osseointegration of hydroxyapatite-coated implants: an experimental study in sheep

Research efforts aim at enhancing early osseointegration of cementless implants to improve early fixation and, thus, reduce the risk of loosening. The aim of the present study was to investigate whether bone morphogenetic protein (BMP) 2 had a positive effect on the osseointegration of hydroxyapatite-coated implants. Hydroxyapatite (HA) implants (perforated hollow cylinders and solid rods) were coated with BMP-2 and hyaluronic acid (HY) as the carrier or with HY alone. Uncoated HA implants served as controls. The osseointegration of the implants was evaluated either by light microscopy or by pullout tests after 1, 2, and 4 weeks of unloaded implantation in the cancellous bone of 24 sheep. The BMP-2 coating significantly increased bone growth into the implant perforations compared with HA-coated implants at 2 and 4 weeks. Bone-implant contact and interface shear strength of BMP-2 implants were lower than HA implants at 2 weeks. At 4 weeks, there was no significant difference in bone-implant contact and shear strength between BMP-2 and HA-coated implants. The BMP-2 coating enhanced gap healing but had no positive or even an inhibitory effect (at 2 weeks) on bone-implant contact and interface shear strength. In the clinical situation, a perfect press-fit implantation cannot be achieved, and BMP-2 may be beneficial for enhancing bone growth into gaps around cementless implants.     

In vivo effects of RGD-coated titanium implants inserted in two bone-gap models

RGD (Arg-Gly-Asp) coating has been suggested to enhance implant fixation by facilitating the adhesion of osteogenic cells to implant surfaces. Orthopedic implants are unavoidably surrounded partly by gaps, and these regions represent a challenging environment for osseointegration. We examined the effects of cyclic RGD-coated implants on tissue integration and implant fixation in two cancellous bone-gap models. In canines, we inserted loaded RGD-coated implants with 0.75-mm gap (n = 8) and unloaded RGD-coated implants with 1.5-mm gap (n = 8) into the distal femur and proximal tibia, respectively. Control gap implants without RGD were inserted contralaterally. The titanium alloy (Ti-6Al-4V) implants were plasma sprayed and cylindrical. The observation period was 4 weeks and the fixation was evaluated by push-out test and histomorphometry. Mechanical implant fixation was improved for RGD-coated implants. Unloaded RGD-coated implants showed a significant increase in bone whereas both loaded and unloaded implants showed a significant reduction in fibrous tissue anchorage. The results are encouraging, because RGD had an overall positive effect on the fixation of titanium implants in regions where gaps exist with the surrounding bone. RGD peptide coatings can potentially be used to enhance tissue integration in these challenging environments.     

Effect of surface finish on the osseointegration of laser-treated titanium alloy implants

It was the purpose of this study to examine the osseointegration of laser-textured titanium alloy (Ti6Al4V) implants with pore sizes of 100, 200, and 300 microm, specifically comparing 200-microm implants with polished and corundum-blasted surfaces in a rabbit transcortical model. Using a distal and proximal implantation site in the distal femoral cortex, each animal received all four different implants in both femora. The bone-implant interface and the newly formed bone tissue within the pores and in peri-implant bone tissue were examined 3, 6, and 12 weeks post-implantation by static and dynamic histomorphometry. Here we show that additional surface blasting of laser-textured Ti6Al4V implants with 200-microm pores resulted in a profound improvement in osseointegration, 12 weeks postimplantation. Although lamellar bone formation was found in pores of all sizes, the amount of lamellar bone within pores was linearly related to pore size. In 100-microm pores, bone remodeling occurred with a pronounced time lag relative to larger pores. Implants with 300-microm pores showed a delayed osseointegration compared with 200-microm pores. We conclude that 200 microm may be the optimal pore size for laser-textured Ti6Al4V implants, and that laser treating in combination with surface blasting may be a very interesting technology for the structuring of implant surfaces.